Acharya Balkrishna, Subarna Pokhrel and Anurag Varshney* Pages 1 - 9 ( 9 )
Background: SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells.
Objective: We have screened phytocompounds from a medicinal herb, Tinospora cordifolia, for their capacities to interrupt the viral RBD and host ACE2 interactions.
Method: We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy.
Results: ‘Tinocordiside’ docked very well at the center of the interface of ACE2-RBD complex, and was found to be well stabilized during MD simulation. Tinocordiside incorporation significantly decreased electrostatic component of binding free energies of ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). As the basal rate constant of protein association is in the order of 5, (105 to 106 M-1 S-1 ), there might be no big conformational change or loop reorganization, but involves only local conformational change typically observed in diffusion-controlled association. Taken together, the increase in global flexibility of the complex, clearly indicates the start of unbinding process of the complex.
Conclusion: It indicates that such an interruption of electrostatic interactions between the RBD and ACE2, and the increase in global flexibility of the complex, would weaken or block SARS-CoV-2 entry and its subsequent infectivity. We postulate that natural phytochemicals like Tinocordiside could be the viable options for controlling SARS-CoV-2 contagion and its entry into host cells.
SARS-CoV-2, COVID-19, ACE2-RBD complex, Tinospora cordifolia, Tinocordiside, Docking, Molecular Dynamics simulation, Electrostatic component of binding free energy.
Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand, Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand, Drug Discovery and Development Division, Patanjali Research Institute, Roorkee-Haridwar Road, Haridwar-249405, Uttarakhand